A single arm study investigating the glycaemic control and safety of adding semaglutide to insulin icodec in participants with type 2 diabetes qualifying for treatment intensification.
- Trial ID
- 2022-502717-28-00
- Protocol
- NN1436-4910
- Sponsor
- Novo Nordisk A/S
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **glycaemic control** achieved through the intensification of treatment with **insulin icodec** in combination with **semaglutide** in patients diagnosed with **Type 2 Diabetes**. This is clinically relevant as optimizing glycaemic control is crucial in managing Type 2 Diabetes, potentially reducing the risk of complications associated with poor blood sugar management.
Secondary objectives include investigating the safety profile of the intensified treatment regimen involving insulin icodec and semaglutide. Understanding the safety is essential to ensure that the benefits of improved glycaemic control do not come at the cost of increased adverse effects, thereby supporting the overall therapeutic strategy for patients with Type 2 Diabetes.
Participants
The clinical trial involves a total of **78 participants** diagnosed with **Type 2 Diabetes**. The study population includes both male and female subjects, aged **18 years and older**, who are not part of a vulnerable population. Participants were selected based on specific criteria, including a diagnosis of Type 2 Diabetes for at least 180 days prior to screening and a **glycated hemoglobin (HbA1c)** level between 7.5% and 10.5% at screening. They are required to have been treated with basal insulin for a minimum of 90 days before screening, without the use of glucagon-like peptide-1 receptor agonists. The participants' **body mass index (BMI)** must be 40.0 kg/m² or less. Lifestyle considerations such as diet and physical activity are not specified, but participants must be willing to adhere to the study protocol, including self-measured plasma glucose profiles. The trial aims to investigate the glycemic control of insulin icodec intensification with semaglutide in these patients.
Plans and Procedures
The clinical trial is designed to evaluate the **glycaemic control** and safety of adding **semaglutide** to **insulin icodec** in participants with **type 2 diabetes** who require treatment intensification. This is a single-arm study with a focus on the intensification of insulin therapy. The trial is expected to last for a total duration of 52 weeks, with participant involvement spanning the same period. The study will employ a **solution for injection** form of both insulin icodec and semaglutide, administered via **subcutaneous injection** using a pre-filled, multi-dose pen-injector.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of type 2 diabetes, and current treatment regimen. The primary inclusion criteria include a **glycated haemoglobin (HbA1c)** level between 7.5% and 10.5%, treatment with basal insulin, and a body mass index (BMI) of 40 kg/m² or less. The study will exclude individuals who do not meet these criteria or who have conditions that may interfere with the study outcomes.
Following the screening visit, participants will attend regular follow-up visits to monitor changes in HbA1c, mean 7-point self-measured plasma glucose (SMPG) profiles, post-prandial glucose increments, and fasting plasma glucose (FPG). Secondary endpoints include the number of severe and clinically significant hypoglycaemic episodes, changes in body weight, and relative changes in weekly insulin icodec dose. The end-of-study visit will assess the overall outcomes and safety of the treatment regimen.
Participants are expected to adhere to the protocol, including self-monitoring of plasma glucose levels. Conditions that may lead to early termination from the study include non-compliance with the study protocol, adverse events, or withdrawal of consent. The trial aims to provide valuable insights into the efficacy and safety of combining semaglutide with insulin icodec for improved glycaemic control in patients with type 2 diabetes.
Treatment
The clinical trial involves the administration of **insulin icodec**, a novel long-acting insulin analog, formulated as a **solution for injection**. The product, known as insulin icodec 700 U/mL PDS290, is manufactured by Novo Nordisk A/S. It is delivered using a disposable, pre-filled, multi-dose pen-injector, specifically the PDS290 pen-injector, which is capable of subcutaneously delivering doses in increments of 10 U. The maximum treatment period for insulin icodec is 52 weeks. The administration route is subcutaneous injection, and the dosing schedule is determined based on the study protocol, with compliance monitored through regular assessments.
In addition to insulin icodec, the trial includes the administration of **semaglutide**, a glucagon-like peptide-1 (GLP-1) receptor agonist, also formulated as a **solution for injection**. The product, Semaglutide B 1.34 mg/mL PDS290, is also produced by Novo Nordisk A/S. It is administered using a prefilled, fixed, multi-dose pen-injector designed for single-patient use, intended for subcutaneous injection. The maximum total dose of semaglutide is 21 mg over a treatment period of 26 weeks. The administration route is subcutaneous, and dosing schedules are adhered to as per the study protocol, with participant compliance being closely monitored throughout the trial.
Efficacy
The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include changes in **glycated haemoglobin (HbA1c)**, mean 7-point self-measured plasma glucose (SMPG) profiles, mean post-prandial glucose increment over all meals, and fasting plasma glucose (FPG). These parameters will be measured to evaluate the glycaemic control achieved by the intensification of insulin icodec with semaglutide in patients with type 2 diabetes.
Secondary endpoints will focus on the safety and additional efficacy aspects, including the number of severe hypoglycaemic episodes (level 3), the number of clinically significant hypoglycaemic episodes (level 2) confirmed by blood glucose meter, changes in body weight, and the relative change in weekly insulin icodec dose. These endpoints will provide a comprehensive assessment of the treatment's impact on the participants' health and safety.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Informed consent obtained before any study-related activities. Study‑related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
- Age above or equal to 18 years at the time of signing informed consent.
- Diagnosed with type 2 diabetes (T2D) greater than or equal to (≥) 180 days prior to the day of screening.
- Glycated haemoglobin (HbA1c) from 7.5 percent (%) ‑10.5 percent (%) (58‑91 millimoles/mole (mmol/mol)) (both inclusive) at screening confirmed by central laboratory analysis.
- Treated with once daily or twice daily basal insulin (minimum of 0.25 International Units (IU)/Kilograms (kg)/day or 20 IU/day) without concomitant glucagon-like peptide-1 receptor agonists (GLP-1 RAs) ≥ 90 days prior to the day of screening with or without any of the following antidiabetic drugs/regimens with stable doses ≥ 90 days prior to screening: Metformin, Sulfonylureas, Meglitinides (glinides), Dipeptidyl peptidase-4 (DPP-4) inhibitors, Sodium-glucose co-transporter-2 (SGLT2 inhibitors), Thiazolidinediones, Alpha-glucosidase inhibitors, Oral combination products (for the allowed individual oral anti-diabetic drugs)
- Body mass index (BMI) less than or equal to (≤) 40.0 kg/m2 (square meters)
- The need and willingness to undergo treatment intensification with the treatments investigated in this study with the aim to reach an HbA1c of 6.5% to 7.5% (48 mmol/mol to 58 mmol/mol) (both inclusive), as assessed by the investigator.
- Ability and willingness to adhere to the protocol including performance of self-measured plasma glucose (SMPG) profiles according to the protocol.
Exclusion Criteria
- Known or suspected hypersensitivity to study intervention(s) or related products.
- Previous participation in this study. Participation is defined as signed informed consent.
- Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive method, as defined in Appendix 4 (Section 10.4).
- Participation (i.e., signed informed consent) in any interventional, clinical study within 90 days before screening. Note: Simultaneous participation in a study with the primary objective of evaluating an approved or non-approved investigational medicinal product for prevention or treatment of COVID-19 disease or postinfectious conditions is allowed if the last dose of the investigational medicinal product has been received more than 30 days before screening in the current study.
- Any disorder, except for conditions associated with T2D, which in the investigator’s opinion might jeopardise participant’s safety or compliance with the protocol.
- Any episodes of diabetic ketoacidosis within 90 days prior to the day of screening
- Presence or history of pancreatitis (acute or chronic) within 180 days before screening.
- Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening and between screening and initiation.
- Chronic heart failure classified as being in New York Heart Association (NYHA) Class IV at screening.
- Planned coronary, carotid or peripheral artery revascularisation.
- Renal impairment with estimated Glomerular Filtration Rate (eGFR) value of eGFR <30 mL/min/1.73m2.20
- Impaired liver function, defined as Alanine Aminotransferase (ALT) ≥2.5 times or Bilirubin >1.5 times upper normal limit at screening.
- Known hypoglycaemic unawareness as indicated by the investigator according to Clarke’s questionnaire question 821 (Section 8.2).
- Recurrent severe hypoglycaemic episodes within the last year as judged by the investigator.
- Inadequately treated blood pressure defined as systolic ≥180 millimetres of mercury (mmHg) or diastolic ≥110 mmHg at screening.
- Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days prior to the day of screening.
- Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g., treatment with orlistat, thyroid hormones, or corticosteroids).
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and initiation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
- Presence or history of malignant neoplasms or in situ carcinomas (other than basal or squamous cell skin cancer, low-risk prostate cancer, or in-situ carcinomas of the cervix or carcinoma in situ/high grade prostatic intraepithelial neoplasia (PIN)) within 5 years before screening.
- Use of any medication with unknown or unspecified content within 90 days before screening.
- Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Not Recruiting | 29 Jan 2024 | 30 |
 Poland | Not Recruiting | 29 Jan 2024 | 40 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
insulin icodec 700 U/mL PDS290 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS INJECTION | 00 | 52 | PRD8146587 |
Semaglutide B 1.34 mg/ml PDS290 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS | 00 | 26 | PRD544503 |